Summary

The following aspects of carbohydrate metabolism were compared in liver and in the transplantable hepatocarcinoma C954 carried by the C57-leaden mouse strain: (a) glucose production from endogenous sources; (b) glucose-6-phosphatase and isomerase activities; (c) glycogen synthesis; (d) extent of glucose utilization for CO2, lactate, and fatty acid formation; (e) pathways of glucose catabolism; and (f) operation of the tricarboxylic acid cycle.

Liver slices produced a large amount of glucose from endogenous sources. No such formation was detected in the experiments with the hepatocarcinoma slices. This inability of the tumor to form glucose from endogenous sources was associated with the absence of gucose-6-phosphatase in homogenates prepared from it. The presence of hexosephosphate isomerase was demonstrated in both tumor and liver. No glycogen synthesis from glucose was observed in slices of the hepatocarcinoma.

The extent of utilization of glucose for lactate and fatty acid formation by liver and tumor slices was studied with various concentrations of labeled glucose in the medium. At all concentrations studied the recoveries of C14 as lactate and fatty acids in the experiments with tumor slices surpassed those observed with liver.

In host liver slices the yields of C14O2, C14-labeled fatty acids, and lactate-C14 from glucose-1-C14 and -6-C14 were approximately equal. In the hepatocarcinoma C954 slices the C14O2 yields from glucose-1-C14 were 2–3 times those from glucose-6-C14. The recoveries of C14-labeled fatty acids and lactate-C14 from glucose-6-C14 exceeded those from glucose-1-C14 in the experiments with the hepatocarcinoma.

The participation of the hexosemonophosphate oxidative pathway in glucose metabolism of this tumor was estimated by two methods. A considerable portion of glucose catabolism in the tumor proceeded via this direct oxidative pathway. It would appear that, in the liver of the tumor-bearing mouse, the Embden-Meyerhof scheme is by far the major pathway for conversion of glucose carbon to fatty acids.

Chromatographic-radioautographic analysis of water-soluble compounds derived from glucose breakdown by the slices of the hepatocarcinoma offers evidence for the operation of the tricarboxylic acid cycle in this neoplasm.

Evidence suggestive of a defect in the conversion of glutamate to glutamine by the hepatocarcinoma is presented.

Footnotes

↵* Aided by grants from the American Cancer Society and in part by the Cancer Research Funds of the University of Calif.